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Nouveaux complexes biomimétiques dérivés de calix[6]azacryptands :étude des effets de seconde sphère et greffage sur surface
No full textMore than 30% of all enzymes present a metal ion in their active site. Interesting sub-families present a mononuclear active site where a single metal ion (Zn2+ or Cun+) is coordinated to a polyhistidine core. The elaboration of model compounds is important for understanding the fundamental mechanisms involved in their bio-catalytic cycles. In this context, we have developed calix[6]arene based ligands presenting an aza cap covalently linked to the calixarene moiety. These supramolecular assemblies present several advantages: they offer a coordination site for a metal ion through the nitrogen donor atoms of the cap, the small rim of the calixarene moiety defines the second coordination sphere, and the hydrophobic cavity presents an access channel for exogenous ligands. In these systems the coordinating nitrogen atoms are separated from the oxygen rich small rim by two carbon atoms, which allows the controlled coordination of one single guest inside the cavity. Wanting to modulate the properties of the calix[6]arene tren-based (tris(2-aminoethyl)amine) ligand, we successfully synthetized several new receptors and studied their reactivity.The synthesis of “two-story” receptors, the calix[6]amido-tren and calix[6]amido-tacn, allowed the modification of the first and second coordination sphere of a coordinated metal ion by introducing an additional spacer between the tripodal aza-cap and the calixarene macrocycle. The complexes of CuI, CuII and ZnII of these new ligands were synthesized and their reactivity was studied. The presence of three potentially coordinating carbonyl groups changed the host-guest reactivity of these metal complexes as they are in competition with exogenous ligands. A comparative study of the host-guest properties and of the reactivity of the metal complexes of both ligands, calix[6]amido-tren and calix[6]amido-tacn was realized. The cavity of these “two-story” ligands is larger than the one of the parent calix[6]tren and more flexible, allowing not only the coordination of an anion, but the simultaneous coordination of two Cl ligands. The oxidation of sterically hindered amines into hydroxylamines and oximes in the presence of O2 was electrochemically realized by the reduction of the cupric center forming a CuII-superoxo adduct as the reactive species. Amine oxidation has been shown for the parent complex, however, the scope of this reaction was limited due to the smaller cavity. The formation of a CuII-superoxo adduct of the calix[6]amido-tren complex was qualitatively evidenced at low temperature upon addition of O2 to the isolated cuprous complex. This type of adduct has attracted much attention in recent years since it is considered to be a reactive intermediate in the catalytic cycle of copper monooxygenases, such as PHM and DβM. A supramolecular assisted demethylation methodology was developed for different capped calix[6]azacryptands. This methodology was then successfully applied to the demethylation of calix[6]tren in order to obtain calix[6]trentrisPhOH. This receptor showed a very different behavior in comparison to the parent one. Indeed, the complexation of anions and biologically relevant ammonium ions was evidenced by the monoprotonated receptor. The metal complexes of CuII and ZnII were synthesized. The interaction between the metal center and the phenate groups in presence of base has been evidenced and has conducted to a multi-step molecular switch. The cupric complex showed the presence of a phenoxyl radical resembling the oxidized form of galactose oxidase, catalyzing the oxidation of alcohols into aldehydes. These results open the way to new perspectives in reactivity studies.An analog of calix[6]tren, bearing a functionalized reactive arm on the tren cap, was synthesized and the corresponding CuII complex was immobilized on a gold surface through a monolayer formation. In organic medium, the host-guest properties of the grafted calix[6]tren are unchanged, while in aqueous medium, a reversible redox system was observed allowing the selective detection of linear alkylamines at basic pH. To our knowledge, this is the first copper supramolecular system immobilized on surface which permits that kind of detection in an aqueous environment.Plus de 30% des enzymes présentent un ion métallique dans leur site actif qui est la clé pour les réactions de catalyse. Une sous-famille d’enzymes comporte un site actif où un seul ion métallique (Zn2+ ou Cun+) est coordiné à un cœur polyhistidine. L’élaboration de composés modèles est important pour la compréhension des mécanismes fondamentaux impliqués dans le cycle biocatalytique de ces enzymes mononucléaires. Dans ce contexte, nous avons développé des ligands basés sur des calix[6]arènes présentant un chapeau polyazoté lié de manière covalente au macrocycle. Ces ligands offrent un site de coordination pour le métal et une cavité hydrophobe bien définie. Cet assemblage permet et contrôle la liaison d’un ligand exogène dans la cavité. Afin de moduler les propriétés des complexes métalliques calixaréniques basés sur une unité coordinante tren (tris(2-aminoéthyl)amine), nous avons synthétisé avec succès et étudié plusieurs nouveaux récepteurs calix[6]aréniques.La synthèse de récepteurs bisétagés, le calix[6]amido-tren et le calix[6]amido-tacn, a permis de modifier la seconde sphère de coordination par incorporation de groupements amide entre la cavité et le site de coordination. Cette stratégie s’est avérée efficace. En effet, la coordination d’anions au centre métallique a été mise en évidence et en particulier celle simultanée de deux Cl pour le Cu-calix[6]amido-tren. Cette coordination d’un ou plusieurs invités anioniques était impossible dans le cas du calix[6]tren parent qui présente une seconde sphère de coordination électroniquement dense et un chapeau trop petit pour y accueillir plusieurs invités. La présence de groupements carbonyle entre la chapeau tren et le calixarène modifie également le comportement des complexes :leur coordination au centre métallique entre en compétition avec celle d’invités exogènes. L’oxydation d’amines encombrées sous O2 en hydroxylamines et oximes a été réalisée par la réduction du complexe cuivrique du calix[6]amido-tren par électrochimie. Ce type d’amines n’est pas oxydable par l’adduit superoxo du complexe parent, dû à la taille de la cavité qui empêche la coordination d’invités encombrés. De plus, la formation d’un adduit superoxo a été mise en évidence qualitativement au départ du complexe cuivreux isolé de ce même composé. Ces résultats permettent d’envisager des études de réactivité mimant le site actif des enzymes PHM et DβM par exemple. Enfin, une comparaison des propriétés hôte-invité et de la réactivité des complexes du calix[6]amido-tren avec celles des complexes du calix[6]amido-tacn a été réalisée afin d’évaluer l’impact de la nature du chapeau polyazoté sur les propriétés hôte-invité et la réactivité de ces complexes.Une méthodologie de déméthylation assistée de manière supramoléculaire a été développée pour différents calix[6]azacryptands chapeautés. Celle-ci a ensuite été appliquée avec succès à la déméthylation du calix[6]tren pour obtenir le calix[6]trentrisPhOH. Ce récepteur a montré un comportement très différent de celui du récepteur parent. En effet, la complexation d’anions et d’ammoniums biologiquement pertinents a été possible par ce récepteur protonné. L’interaction entre le centre métallique et les phénates en présence de base a conduit à la réalisation d’un switch moléculaire multi-étapes entre différents états de protonation du récepteur et du complexe zincique. Son complexe cuivrique a montré la présence d’un radical phénoxyle après oxydation du phénate. Cette espèce CuII-radical phénoxyle mime la forme oxydée du site actif de la galactose oxydase, catalysant l’oxydation d’alcools en aldéhydes. Ces résultats ouvrent donc la voie à de nouvelles perspectives pour les études de réactivité de ce composé.Un analogue du calix[6]tren, porteur d’un bras avec une fonction réactive sur le chapeau, a été synthétisé et complexé au cuivre avant d’être immobilisé sur surface via la formation de monocouches. Les électrodes ainsi modifiées ont été étudiées en milieu organique et aqueux. En milieu organique, les propriétés hôte-invité du calix[6]tren sont conservées après immobilisation. En milieu aqueux, un système redox réversible a été observé. Celui-ci a permis la détection sélective d’alkylamines linéaires par le système à pH basique. A notre connaissance, il s’agit du premier système supramoléculaire à cuivre, immobilisé sur surface, qui permet cette détection en milieu aqueux.Doctorat en Sciencesinfo:eu-repo/semantics/nonPublishe
European Muslims and Liberal Citizenship: Reconciliation through Public Reason: The Case of Tariq Ramadan's Citizenship Theory
No full textThis study investigates the subject of Muslims’ citizenship in contemporary Western European societies from the viewpoint of John Rawls’s political liberalism, in particular in light of the ‘idea of public reason’ [see John Rawls, Political Liberalism, expanded edition (New York: Columbia University Press, 2005) and the 1997 essay “The Idea of Public Reason Revisited,” originally published in University of Chicago Law Review 64 (1997), 765-807 and now included in Political Liberalism, expanded edition, 440-490]. By its very nature, political liberalism does not prescribe a single model for being Muslim in contemporary Europe. Thus, one may wonder if it is too vague as a point of departure for the analysis. On the other hand, however, here I argue that political liberalism specifies a peculiar evaluative framework that allows citizens to answer questions such as “What is politically at stake when citizens of Muslim faith are publicly presented as permanent aliens in contemporary European societies?”, “On what grounds is such exclusion based?”, and “What requirements can European citizens be reasonably expected to meet?” in a distinctively political way and, ideally, to solve the political and social problems from which those questions spring. In this research, I claim that public reason provides a common discursive platform that establishes the ground for a public political identity and for shared standards for social and political criticism. Together, these two elements solve the two dimensions of the problem of ‘stability for the right reasons’ (in Rawls’s terms) in contemporary European societies, because they secure both the political inclusion of Muslims on an equal footing as citizens and civic assurance that they will remain committed to fair terms of social cooperation. A joint solution of these two apparently conflicting demands of stability for the right reasons (i.e. inclusion and mutual assurance) requires an effort in political reconciliation. After having compared public reason citizenship with two prominent normative alternatives, I will conclude that the former is an adequate ideal conception of citizenship for European societies. Finally, I will apply the justificatory evaluative methodological framework (whose requirements I will specify starting from the idea of public reason itself) to a conception of citizenship elaborated by one of the most renowned Muslim public intellectuals in Europe: Tariq Ramadan. (I justify the choice of this author in sections 2.3 and 6.1). Such an evaluation sheds light on one of the main insights of this research, that is, the idea that public reason makes a decompression of the public space possible: it frees the public space from those forces that would prevent citizens from the possibility of exercising effectively their two moral powers (once more in Rawls’s words, the ‘capacity for a sense of justice and for a conception of the good’) as free equals. In this sense, public reason tries to reconcile ideal political consensus and the fact of reasonable pluralism on a public political ground. I believe that this is the deepest meaning of what Rawls calls ‘reconciliation through public reason’: its aspiration is to reabsorb reasonable pluralism politically without annihilating it.This research is structured in three parts: the first is methodological, the second is reconstructive, and the third is evaluative. Each part is composed of two chapters.In chapter one (“General Framework”), I begin from some empirical observations about the role of perceptions and identities in relation to the issue of Muslims’ citizenship in contemporary Europe. I claim that from this point of view Islam seems to “make problem” in a very specific sense. This does not mean that Islam is a problem, but that Islam is frequently publicly presented and perceived as a problem. This is the background problem from which my work starts. Thus, I explore some dimensions of such a problem (see 1.1). Subsequently, I provide a more specific formulation of the research problem and questions and of the aims of this study. Then, the main research question (Q) is stated in these terms: Which ideal conception of citizenship should provide the common normative perspective in contemporary Western European societies, which are characterised by both demands of inclusion of Muslims and the need for solving a ‘problem of mutual assurance’ [on which, see in particular Paul Weithman, Why Political Liberalism? On John Rawls’s Political Turn (New York: Oxford University Press, 2010)] concerning citizens’ commitment to shared terms of social cooperation, so that those societies can be stable for the right reasons? In order to answer this question, I also specify three sub-questions that I call respectively Q1, Q2, and Q3 (see 1.2).In chapter two (“Toward a Justificatory Evaluative Political Theory”), I firstly try to frame the problem of public justification within Rawls’s political liberalism (see 2.1). I then consider a specific approach to the question of Muslim citizenship in liberal democracies which can be adopted from a Rawlsian perspective: namely, reasoning from conjecture (see 2.2). Finally, I explain my own approach (which I call justificatory evaluative political theory) by means of comparison with the method of reasoning from conjecture (see 2.3). In presenting the evaluative framework specified from a political liberal standpoint, I point out three political liberal evaluative requirements: the reciprocity requirement (RR), the consistency requirement (CR), and the civility requirement (CiR).Chapter three (“What is Public Reason?”) deals with the history of the notion of public reason from Kant to Rawls and its enunciation within Rawls’s work (see 3.1 and 3.2 respectively). In doing so, I also identify three specifications for the three political liberal evaluative requirements considered in the second chapter. Furthermore, in chapter three I also unpack CR in three different dimensions (PR1, PR2, and PR3).Chapter four (“Public Reason and Religion. Reinterpreting the Duty of Civility”) completes the reconstructive stage by analysing Rawls’s ‘wide view’ of public reason and two major lines of objection to it (see 4.1). After having discussed such criticisms, I then introduce my own interpretation of the ‘proviso,’ which is structured around a two-level (or bifurcate) model of the ‘duty of civility’ (see 4.2).Chapter five (“Reconciliation through Public Reason: Justificatory Evaluative Political Theory between Modelling and Application”) bridges the second and the third part, that is, the reconstructive and the evaluative stage respectively. In the first section of the chapter, I summarise the political liberal evaluative requirements developed in the second part. In doing this, my purpose is to present my justificatory evaluative model of public reason citizenship (see 5.1). In the second section, I firstly argue that a conception of citizenship grounded in public reason is not only possible in existing European societies, but also preferable if compared with alternative conceptions (I consider liberal multiculturalism and Cécile Laborde’s critical republicanism [Cécile Laborde, Critical Republicanism: The Hijab Controversy and Political Philosophy (Oxford: Oxford University Press, 2008)]) with reference to the problem under scrutiny in this research. In conclusion, I show that public reason citizenship is able to solve the theoretical problem and the main research question mentioned above: Which ideal conception of citizenship should provide the common normative perspective in contemporary Western European societies, which are characterised by both demands of inclusion of Muslims and the need for solving a problem of mutual assurance concerning citizens’ commitment to shared terms of social cooperation, so that those societies can be stable for the right reasons? In the final part of chapter five, I try to demonstrate that public reason citizenship can both include Muslim citizens and solve the assurance problem because it provides both shared standards for political criticism and a common political identity on the basis of which citizens politically recognise one another as free equals. If my argument succeeds, then public reason citizenship not only could but also should be adopted as the ideal conception of citizenship in European societies (see 5.2).In the sixth chapter (“Tariq Ramadan’s European Muslims and Public Reason”) I apply the evaluative framework based on public reason to the conception of citizenship for Muslims in Europe developed by Tariq Ramadan. (According to a principle introduced in chapter two which I call the “plausibility principle” PP, I argue that Ramadan’s theory of citizenship can be plausibly presented as a “European Muslim” approach to the issue of citizenship, see 6.1). The purpose of such an evaluative work is twofold. Firstly, it aims at examining whether and how the idea of public reason accounts for a version of European citizenship for Muslims coming from Muslims themselves. Secondly, it aims at disclosing whether what such a Muslim conception of citizenship in Europe says about the two dimensions of ‘stability for the right reasons’ of the system of social cooperation (namely, inclusion and ‘mutual assurance’) is consistent with the provisions of public reason citizenship (see 6.2-6.5).Doctorat en Sciences politiques et socialesN.B. 1) Le lieu de défense de la thèse en cotutelle est ROME (Luiss Guido Carli)2) L'affiliation du co-promoteur de la thèse en cotutelle (Sebastiano Maffettone) est: LUISS Guido Carliinfo:eu-repo/semantics/nonPublishe
Le patrimoine subaquatique du lac Titicaca, Bolivie. Utilisation et perception de l’espace lacustre durant la période Tiwanaku (500-1150 PCN)
No full textDepuis plus de 30 ans, de nombreux projets de recherches ont mis en évidence une occupation dense et complexe du bassin lacustre du Titicaca, et en particulier celle de la période Tiwanaku entre le 5e et le 11e siècle de notre ère. Celle-ci sera la première à modifier profondément le paysage lacustre en y laissant une empreinte matérielle indélébile. L’utilisation des plaines, des vallées et des élévations naturelles connectées ou surplombant le lac est donc physiquement marquée par l’occupation de cette culture. Or, l’utilisation ancienne de ces espaces s’arrête-t-elle à la frontière entre la terre ferme et cette vaste étendue d’eau ? Dans le cadre de ce projet de recherche, nous proposons d’élargir - au sens propre et figuré - l’étude de la culture Tiwanaku en agrandissant le territoire usuellement étudié grâce à l’intégration de deux espaces dont l’utilisation ancienne est encore à l’heure actuelle totalement méconnue : l’espace littoral (les côtes) et l’espace lacustre (le lac). La mise en place d’un projet de recherche utilisant les techniques de plongée devenait donc nécessaire et inévitable pour étudier les témoignages matériels directs de l’utilisation du lac par l’homme, et de sa signification pour les populations de la période Tiwanaku. Les conditions naturelles favorables ont motivé les premiers peuplements des rives et des îles, et le lac a progressivement fait partie de l’identité des populations qui s’y sont installées. Que ce soit sur le plan politique, socioculturel ou rituel, le lac a eu une incidence sur l’évolution de ces populations et a favorisé l’émergence de pratiques indissociables d’un espace lacustre. Les géostratégies d’occupation du territoire en sont tributaires, ainsi que les stratégies de subsistance, de vie et de survie, notamment durant les périodes de crise. Sur le plan rituel et sacré, cette « mer intérieure » faisait partie du quotidien et, en tant que telle, a joué un rôle prépondérant dans la relation qu’entretenait l’homme avec l’espace dans lequel il vivait. Il a rationalisé cet espace pour le comprendre (croyances, mythes, etc.), a développé des schémas et des objets symboliques pour le représenter (iconographie, offrandes, etc.), et a créé des rites pour l’entretenir. Dans le cadre de ce projet de recherche, nous proposons principalement d’aborder l’utilisation et la perception de l’espace lacustre Tiwanaku grâce à l’analyse des pratiques d’offrandes subaquatiques de céramiques rituelles de type incensario, en comparaison avec celles attestées sur la terre ferme. Un site d’offrandes sous l’eau ne peut pas en effet être analysé de manière isolée, car il met en évidence des pratiques rituelles du passé en relation avec d’autres espaces non immergés. Les sites d’offrandes représentent par conséquent des espaces d’étude privilégiés, car ils documentent directement la relation de l’homme de Tiwanaku avec son environnement, et en particulier le lac.Doctorat en Histoire, histoire de l'art et archéologieinfo:eu-repo/semantics/nonPublishe
Migration, human capital, and growth in a globalized economy
Full text linkThis thesis focuses on the implications of past, and hypothetical future movements of people for the prosperity of natives and residents living in the highly developed regions. The first Chapter discusses the welfare impact of migration in the OECD countries by analyzing recent migration flows (net migration between 2000 and 2010), and total stock of migrants in 2010. The importance of different channels, through which migration affects the wellbeing of stayers, is discussed. In the second Chapter, the theoretical framework from the first Chapter is extended to evaluate migration policies in a multi-country general equilibrium model with endogenous migration and trade. In particular, the economic impact of removing visa and trade barriers between the European Union and five major partners (Australia, Canada, Japan, Turkey and the US) is quantified. Additionally, the proposed model gives theoretical evidence about the relations between migration and trade after imposing exogenous shocks to both types of barriers. The third Chapter proposes an innovative modeling technique to identify the global demographic impact of different migration policies in the EU. The model jointly considers peoples’ endogenous decisions about the country of destination, type of visa to apply for, and the duration of stay. In consequence, the proposed framework provides a micro-foundation for multilateral resistance to migration (a complex structure of dependencies between migration choice options). The research question posed in this paper challenges the capacity of the European Union to attract high-skilled immigrants.(ECGE - Sciences économiques et de gestion) -- UCL, 2016Accès libre18/04/2016(ECGE - Sciences économiques et de gestion) -- UCL, 2016Anglai
Agricultural market failures and peasants’ welfare in South-Kivu
No full textThis research develops the analysis of the incidence of agricultural markets failures on peasants’ welfare in South Kivu, a highly specific equatorial environment made of high mountains, sizeable plains and combining mining and farming activities. Agricultural markets imperfections are key elements explaining the inefficient production and commercialization of food products. Our empirical study, the first of this kind ever made in South Kivu, is based on a personal survey of four territories. A stratified sample of 780 households among which 586 producers and 194 consumers has been built. The first chapter is a two stage analytical process. Market failures and inadequate transport infrastructures are studied in a system of interconnected markets.The data collected in Idjwi and Kalehe are used to test the predictions of the theoretical model. An improvement of transport infrastructures and a decrease in transaction costs increase peasants’ welfare, but only if productive capacities are sufficient. The cassava and the banana are basic commodities in South-Kivu, being extensively cultivated by the farmers. The second chapter analyzes the cassava supply and its price elasticity in a situation of market failures. The results indicate that farmers are fairly insensitive to price changes because of the high transactions costs. The third chapter analyzes the choice between selling at the farm or on the market.The endogenous switching regression model used in this chapter show that farmers’ choices are crucially dependent on transaction costs and that the intermediaries’ collusions on price are not always stable. Chapter four discusses the various policies to support production and value chains. Agricultural cooperatives networks, policies of improving infrastructures and an adequate institutional regulatory framework to monitor the market exchange processes, especially the role of intermediaries, are key points.(AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 2016Accès interdit04/03/2016(AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 2016Anglai
Le transfert de l’exécution des peines privatives et restrictives de liberté en droit européen :à la recherche d’un équilibre entre intérêts individuels et collectifs
No full textThe transnational enforcement of sentences to deprivation or restriction of liberty involves multiple interests that may vary according to the point of view which is taken into consideration: the stance/angle of the offender, of the sentencing State, or of the executing State. These interests are difficult to reconcile. In addition, the execution of – or inversely, the refusal to enforce – a foreign sentence to deprivation or restriction of liberty may also conflict with fundamental rights, such as the prohibition of torture and inhuman or degrading treatment, the right to liberty, the right to a fair trial or the protection of family life. The purpose of this research is twofold: to shed light on the place reserved for these different interests and rights; then to observe how they are concretely articulated and whether they are balanced. Our postulate is that European cooperation on enforcement of sentences to deprivation or restriction of liberty will be neither effective nor legitimate if it fails to achieve such a balance.L’exécution transnationale des peines privatives et restrictives de liberté met en jeu des intérêts divers – et parfois difficilement conciliables – selon que le processus est envisagé du point du vue du condamné, de l’Etat de condamnation ou de l’Etat d’exécution. En outre, l’exécution – ou inversement, le refus d’exécution – d’une condamnation étrangère à une peine privative ou restrictive de liberté peut aussi se heurter à différents droits fondamentaux, qu’il s’agisse de l’interdit de la torture et des traitements inhumains ou dégradants, du droit à la liberté individuelle, des exigences du procès équitable ou encore de la protection de la vie familiale. L’objet de la recherche est de mettre en lumière, la place réservée à ces différents intérêts et droits, la manière dont ils sont concrètement articulés et les évolutions qui se sont dessinées dans le temps. Il s’agit notamment d’observer comment ceux-ci parviennent à s’équilibrer, le postulat de départ étant qu’une coopération européenne en matière d’exécution des peines privatives et restrictives de liberté ne pourra être ni efficace ni légitime si elle ne parvient pas à atteindre cet équilibre.(DROI - Sciences juridiques) -- UCL, 2016Accès interdit24/02/2016(DROI - Sciences juridiques) -- UCL, 2016Françai
Coverings, factorization systems and closure operators in the category of quandles
Full text linkQuandles are mathematical structures that have been mostly studied in knot theory, where they determine a knot invariant that is complete up to orientation. The aim of this thesis is to capture some categorical properties of the variety of quandles. More specifically, we study two adjunctions in the variety of quandles: the first one with its subvariety of trivial quandles and the second one with its subvariety of abelian symmetric quandles. We show that both of them are admissible in the sense of the categorical Galois theory developed by G. Janelidze, and we characterize the corresponding coverings. In particular, we show that the coverings arising from the adjunction with the subvariety of trivial quandles correspond to the quandle coverings introduced and studied by M. Eisermann. We prove that the category of quandle cove- rings is a reflective subcategory of the category of surjective quandle homomorphisms, and we give an explicit description of this reflection. We also investigate some factorization systems for surjective quandle homomor- phisms as well as closure operators of subobjects in the variety of quandles.(SC - Sciences) -- UCL, 2016Accès libre15/01/2016(SC - Sciences) -- UCL, 2016Anglai
Endothelial cells and epithelial BMP signaling control thyroid folliculogenesis via basement membrane assembly
No full textThe thyroid gland is composed of spherical units called the follicles. Follicles are delineated by a monolayer of polarized thyrocytes surrounding the colloidal space, and resting on a basement membrane. Folliculogenesis occurs during embryonic development by reorganization of an unstructured mass of non-polarized cells, but regulatory mechanisms remain largely unknown. Using thyroid-specific VegfaKO and Smad1/5dKO, we show that the absence of endothelial cells or of epithelial BMP signaling prevent follicle formation. Furthermore, these KO thyroids displayed impaired basement membrane assembly. Interestingly, medium conditioned by embryonic endothelial progenitor cells (eEPC) rescues the folliculogenic defects of both KO thyroids. Laminin α1β1γ1, abundantly released by eEPC into the culture medium, is critically required for folliculogenesis. These results indicate that endothelial cells and epithelial BMP signaling promote folliculogenesis via assembly of the basement membrane.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2016Accès embargo15/02/2016(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2016Anglai
Yeast Gdt1 is a Golgi-localized calcium transporter required for stress-induced calcium signaling and protein glycosylation
No full textCalcium signaling depends on a tightly regulated set of pumps, exchangers, and channels that are responsible for controlling calcium fluxes between the different subcellular compartments of the eukaryotic cell. It have been recently reported in our lab that two members of the highly-conserved UPF0016 family, human TMEM165 and budding yeast Gdt1p, are functionally related and form a new group of Golgi-localized cation/Ca2+ exchangers. Both share topological characteristics reminiscent of the cation/calcium exchanger superfamily. They are composed of two hydrophobic regions containing a highly conserved motifs separated by a large cytosolic loop. Defects in the human protein TMEM165 are known to cause a subtype of Congenital Disorders of Glycosylation. The Ca2+ transport activity of Gdt1p was demonstrated using an assay based on the heterologous expression of GDT1 in the bacterium Lactococcus lactis. The Ca2+ uptake activity in cell expressing GDT1 was dependent on the external pH, indicating that Gdt1p may act as a Ca2+/H+ antiporter. This work focuses on the functional and structural study of Gdt1p in the yeast Saccharomyces cerevisiae. We firstly found that Gdt1p controls cellular calcium content and plays a major role in the calcium response following an osmotic shock when the Golgi calcium pump, Pmr1p, is absent. Importantly, we also discovered that, in the presence of a high concentration of external Ca2+, Gdt1p is required for glycosylation of carboxypeptidase Y and the glucanosyltransferase Gas1p. Additionally, we highlighted that Gdt1p levels are controlled by external Ca2+ via a mechanism involving the calcineurin signaling pathway along with vacuolar proteolysis. Finally, by site-directed mutagenesis and characterization of the mutants, we found that the cations binding pocket of Gdt1p is most likely composed of glutamate, aspartate, serine and threonine residues located in the repeated motifs.(AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 2016Accès embargo20/01/2016(AGRO - Sciences agronomiques et ingénierie biologique) -- UCL, 2016Anglai
Implication des neurones striatonigraux et striatopallidaux dans l'apprentissage instrumental séquentiel par ciblage optogénétique
No full textLes circuits neuronaux des noyaux de la base sont impliqués dans la planification et la sélection des mouvements, dans des processus motivationnels et de renforcement, mais aussi dans des fonctions plus cognitives telles que les processus d’apprentissages instrumentaux. Le dysfonctionnement de ces noyaux entraîne des troubles moteurs graves, telles les maladies de Parkinson et Huntington, et des pathologies plus psychiatriques, comme les phénomènes de dépendances aux drogues, le syndrome Gilles de la Tourette ou encore les troubles déficitaires de l’attention avec hyperactivité. Le striatum, structure d’entrée du système des noyaux de la base, est composé en large majorité de neurones de projections GABAergiques épineux de taille moyenne (medium spiny neuron, MSN), qui sont subdivisés en deux populations: les neurones striatonigraux et les neurones striatopallidaux. Ces neurones forment des voies fonctionnelles parallèles et distinctes :celles ci prennent naissance au niveau du striatum après réception de l’information émanant du cortex, puis traversent les autres ganglions de la base (Globus Pallidus, Noyau sous-thalamique, Substance noire), qui ensuite aboutissent sur le thalamus qui retourne l’information traitée aux différentes aires corticales concernées. Ces neurones de projections sont morphologiquement identiques et distribués de manière homogène dans l’ensemble du striatum, rendant difficile leur étude spécifique sans outils génétiques.Dans ce travail, nous avons étudié les rôles respectifs de ces deux populations neuronales dans l’apprentissage instrumental séquentiel par une approche optogénétique. Cette technique permet de contrôler optiquement, à une échelle de temps physiologique et de façon réversible, l’activité d’une population de neurones génétiquement ciblée pendant un comportement. Dans un premier temps, nous avons développé des modèles de souris dans lesquelles chacune de ces deux populations est spécifiquement ciblée au moyen du système Cre/LoxP et à l’aide d’injection stéréotaxique de vecteurs viraux permettant l’expression de canaux photosensibles, comme la Channelrhodopsine-2 (ChR2). Une validation de la fonctionnalité de cette protéine dans ces modèles a d’abord été établie ex vivo par des moyens électrophysiologiques (enregistrement de l’activité des neurones sur tranche de cerveau en survie), puis in vivo, par induction d’un comportement rotatoire caractéristique de l’activation unilatérale de ces populations neuronales.Dans un second temps, ces souris ont été étudiées dans un paradigme comportemental lié au striatum dorsal :l’apprentissage instrumental séquentiel. En effet, l’exécution d’une séquence d’actions dans un ordre bien déterminé est fondamentale pour adopter un comportement adapté. Au cours de l’acquisition d’une nouvelle séquence, chacune de ces deux populations de neurones est activée par optogénétique afin de déterminer leur effet dans cet apprentissage. Nous nous sommes particulièrement intéressés à ces neurones dans le striatum dorsolatéral (DLS), car cette région joue un rôle fondamental dans la formation d’une habitude, et plus particulièrement lors d’un apprentissage séquentiel. Ce travail a pu mettre en évidence l’importante implication respective de ces neurones du DLS lors de l’acquisition d’une séquence puisque nous avons montré que l’activation des neurones striatonigraux facilitait l’apprentissage d’une nouvelle séquence, alors que l’activation des neurones striatopallidaux perturbe cet apprentissage. De plus, nos résultats indiquent que la stimulation optogénétique des neurones striatopallidaux entraîne un déficit à différencier et à associer des actions pour former une unité performante, tandis que l’activation des neurones striatonigraux semble fondamentale pour initier et terminer correctement une séquence. Ces résultats contribuent ainsi à la compréhension du rôle des deux voies principales du striatum dorsolatéral lors d’un apprentissage instrumental séquentiel.Doctorat en Sciences biomédicales et pharmaceutiques (Médecine)info:eu-repo/semantics/nonPublishe